We report a general method for the synthesis of chiral thiosquaramides, a class of bifunctional catalysts not previously described in the literature. Thiosquaramides are found to be more acidic and significantly more soluble in nonpolar solvents than their oxosquaramide counterparts, and they are excellent catalysts for the unreported, enantioselective conjugate addition reaction of the barbituric acid pharmacaphore to nitroalkenes, delivering the chiral barbiturate derivatives in high yields and high enantioselectivities, even with catalyst loadings as low as 0.05 mol%.

We report the intermolecular palladium-catalyzed reaction of tert-butyl propargyl carbonate with tryptamine derivatives or other indole-containing bis-nucleophiles. The reaction proceeds under mild conditions and with low catalyst loadings to afford novel spiroindolenine products in good to high yields.

A set of general methods for the palladium-catalyzed decarboxylative C3-allylation and C3-benzylation of indoles, starting from the corresponding N-alloc and N-Cbz indoles, respectively, is reported. This chemistry provides ready access to a wide range of functionalized indolenines in good to excellent yields. A tandem process, wherein the palladium catalyzed allylation chemistry is coupled with a Mizoroki-Heck reaction, offers a simple route to diverse cinnamylated products.

Reported here are methods for the direct construction of a range of spirocyclized oxindoles and indolenines in good to excellent yields. Specifically, we report the palladium-catalyzed reactions of oxindoles and indoles, both functioning as bis-nucleophiles, with propargyl carbonates to afford spirocyclic products having an exocyclic double bond on the newly formed ring. The reaction proceeds through a process wherein the first nucleophilic unit on the oxindole or indole reacts with an allenyl-palladium species, formed from oxidative addition of Pd(0) to propargyl carbonates, to generate a π-allyl palladium intermediate that then reacts further with the second nucleophilic component of the oxindole or indole. The cascade process forges two bonds en route to spirocyclized oxindole and indolenine products. The use of chiral phosphines renders the cyclization sequence enantioselective, providing spirocyclic products with modest to good enantioselectivities.

We report here a novel method for the modular synthesis of highly substituted piperazines and related bis-nitrogen heterocycles via a palladium-catalyzed cyclization reaction. The process couples two of the carbons of a propargyl unit with various diamine components to provide nitrogen heterocycles in generally good to excellent yields and high regio- and stereochemical control.